Negative autoregulation of RANKL and c-Src signaling in osteoclasts

Abstract

Listen

Translate article

Osteoclasts are multinucleated giant cells that are responsible for bone matrix degradation. The mechanisms of differentiation and bone resorption processes in osteoclasts have been investigated extensively at the molecular level. In particular, the discovery of the receptor activator of the nuclear factor-κB ligand (RANKL) signaling cascade built the foundation for subsequent studies to understand the various aspects of osteoclasts. RANKL, as an essential factor for differentiation and bone resorption, regulates a number of molecules to orchestrate differentiation as well as the function of osteoclasts. Most of those molecules have been proven to play positive roles in osteoclastogenesis and/or bone resorption; however, studies showing that RANKL could also induce autoregulatory signals and modulate its own signaling cascades have been accumulating. Such a regulatory mechanism(s) may contribute to prevent the excess formation and activation of osteoclasts and thereby, to control bone metabolism as a whole. We newly identifi ed such a mechanism in c-Src, and its signifi cance is discussed in the context of RANKL-induced osteoclastogenesis. RANKL signaling in osteoclastogenesis